DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

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SECTION IX
SPECIAL SYSTEMS PHARMACOLOGY
Finasteride is approved for use only in men. Pregnant women
should not be exposed to the drug because of the potential for
inducing genital abnormalities in male fetuses. Adverse effects of
finasteride include decreased libido, erectile dysfunction, ejaculation
disorder, and decreased ejaculate volume. Each of these
occurs in <2% of patients (Leyden et al., 1999). Like minoxidil,
treatment with finasteride must be continued, or any new hair
growth will be lost.
TREATMENT OF HYPERPIGMENTATION
The agents mentioned in this section are most effective
on hormonally or light-induced pigmentation within the
epidermis. They have limited efficacy on post-inflammatory
pigmentation within the dermis.
Hydroquinone. Hydroquinone (1,4-dihydrobenzene; TRI-LUMA) is
the first-line agent in medical therapy of hyperpigmentation. It
decreases melanocyte pigment production by inhibiting the conversion
of dopa to melanin through inhibition of the enzyme
tyrosinase. Other mechanisms include inhibition of DNA and
RNA synthesis, degradation of melanosomes, and destruction of
melanocytes. There are multiple formulations, to which penetration
enhancers, microsponges, and sunscreen ingredients are
added. Adverse effects may include dermatitis and ochronosis;
patients should be followed regularly while on hydroquinone
(Draelos, 2007).
Monobenzone. Monobenzone (BENOQUIN), the monobenzyl ether of
hydroquinone, causes permanent hypopigmentation and should not
be used for routine hormonally induced or post-inflammatory hyperpigmentation.
Azelaic. Azelaic acid (AZELEX, FINACEA) is a dicarboxylic acid isolated
from cultures of Pityrosporum ovale. It was developed through
study of the hypopigmentation produced by infection with P. ovale
(tinea versicolor). It also inhibits tyrosinase activity but is less effective
than hydroquinone. Because it has mild comedolytic, antimicrobial,
and anti-inflammatory properties, it also is often used in
acne and papulopustular rosacea (Draelos, 2007).
Mequinol, also known as 4-hydroxyanisole, methoxyphenol,
hydroquinone monomethyl ether, or p-hydroxyanisole, is a competitive
inhibitor of tyrosinase. It is available as a 2% prescription product
(SOLAGE) in combination with 0.01% tretinoin and vitamin C to
enhance skin lightening (Draelos, 2007).
MISCELLANEOUS AGENTS
Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is an alkaloid
derived from plants of the Solanaceae family (i.e., hot chili peppers).
H 3 C
Capsaicin interacts with the transient receptor potential vanilloid
(TRPV1) receptor on C-fiber sensory neurons. TRPV1 is a
ligand-gated nonselective cation channel of the TRP family, modulated
by a variety of noxious stimuli (Wang, 2008). Chronic exposure
to capsaicin first stimulates and then desensitizes this channel to capsaicin
and diverse other noxious stimuli. Capsaicin also causes local
depletion of substance P, an endogenous neuropeptide involved in
sensory perception and pain transmission. Capsaicin is available as
a 0.025%, 0.035%, 0.075%, 0.1%, and 0.25% cream (ZOSTRIX, others);
0.025% and 0.075% lotion (CAPSIN); 0.025% and 0.05% gel;
0.075% roll-on; and 0.025% transdermal patch. Capsaicin is FDA
approved for the temporary relief of minor aches and pains associated
with backache, strains, and arthritis and is used for off-label
treatment of postherpetic neuralgia and painful diabetic neuropathy.
It is being investigated for psoriasis, vitiligo, intractable pruritus, and
other disorders.
Podophyllin (podophyllum resin) is a mixture of chemicals
from the plant Podophyllum peltatum (mandrake or May apple). The
major constituent of the resin is podophyllotoxin (podofilox). It
binds to microtubules and causes mitotic arrest in metaphase.
Podophyllum resin (10-40%) is applied by a physician and left in
place for no longer than 2-6 hours weekly for the treatment of
anogenital warts. Irritation and ulcerative local reactions are the
major side effects. It should not be used in the mouth or during pregnancy.
Podofilox is available as a 0.5% solution for home application
twice daily for 3 consecutive days. Weekly cycles are repeated until
clearance or for a maximum of four cycles.
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